Heterocyclic, aromatic and cycloalkyl 4-piperidinol esters and related piperidines have been synthesized for study of their action on the central nervous system. Several compounds displayed analgesic activity in the codeine-morphine range in the mouse hot-plate assay. In structure-activity comparisons in this system, aromatic esters exhibited plus Es minus pi substituent effects. In general, the piperidinol esters showed no morphine-like physical dependence capacity in monkeys, acting neither as typical narcotic agonists nor antagonists. In rat brain homogenates in vitro, they displayed marginal to no binding to the opiate receptor.